Camptothecin (camptothecin, CPT, IUPAC name: (S)-4-ethyl-4-hydroxy-1H-pyrano[3′,4′:6,7]indolizino[1,2-b]quinoline-3,14-(4H,12H)-dione) is a alkaloid compound extracted from Camptotheca acuminata (Nyssaceae, China) in 1966 firstly by Wall et al. [J. Am. Chem. Soc. 1966, 88 (16), 3888-990]. It demonstrates anti-tumor activities, particularly against leukemia and numerous solid tumors in experiments, and is a natural cytotoxic compound. By 1970s, phase I and phase II clinical trials have been carried out, and it was found that even though CPT has anti-tumor activity, it has many side effects as well. The side effects include bone marrow suppression, gastrointestinal toxicity, hemorrhagic cystitis, hair loss, diarrhea, nausea, and vomiting, etc.
In order to obtain camptothecin derivatives with high activity and low toxicity, structure modifications and optimizations have been carried out and a series of camptothecin derivatives were synthesized by semisynthesis and total synthesis methods. In 1994, FDA approved a camptothecin derivative (or named as “a camptothecin compound”), irinotecan (Irinotecan, CPT-11), for the treatment of colorectal cancer. In 1996, topotecan (Topotecan) was approved for the treatment of ovarian cancer, and further approved in 1999 by FDA as a second-line medicine for the treatment of small cell lung cancer (SCLC). Nowadays, there are more than ten camptothecin compounds in clinical trials.
Camptothecin is the second anticancer drug extracted from plants after paclitaxel. Since camptothecin compounds exhibit remarkable curative effects, broad anti-tumor spectrum, no cross resistance with other anticancer drugs, they have become one of the most widely used anti-tumor drags in clinical. However, the current camptothecin compounds still exhibit obvious side effects. Thus, improving activities and reducing toxicities of camptothecin compounds are the key targets of research.